Beta-Methyl Carbapenem Stability Against Hydrolysis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The development of effective carbapenem compounds is hindered by the hydrolysis of the β-lactam ring and low recovery rates, leading to limited antibacterial activity against gram-negative bacteria, including drug-resistant strains.
Innovation Solution
The development of novel β-methyl carbapenem compounds with specific structural modifications, such as the general formula (I), which include various substituents and pharmacologically acceptable salts or prodrugs, to enhance stability and antibacterial efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional carbapenem compounds are used, then antibacterial activity is achieved, but the β-lactam ring undergoes hydrolysis and recovery rates are low
Solution Approach 1:
The patent applies parameter changes by introducing a methyl group at the β-position (position 1) of the carbapenem ring structure. This structural modification changes the chemical parameters of the molecule, specifically blocking the hydrolysis pathway of the β-lactam ring while preserving the antibacterial activity. The β-methyl substitution prevents nucleophilic attack at the β-carbon, thereby stabilizing the compound against hydrolysis and improving recovery rates.
2Reliability
If carbapenem compounds are used to treat bacterial infections, then antibacterial activity is achieved, but activity against gram-negative bacteria is limited
Solution Approach 1:
The patent applies local quality by introducing specific substituents at particular positions on the carbapenem core structure. The β-methyl group and additional substituents at positions 2, 3, 4, and 5 create localized structural features that enhance penetration through gram-negative bacterial cell membranes and increase affinity for bacterial targets. This localized structural optimization extends the antibacterial spectrum to include gram-negative bacteria while maintaining activity against gram-positive bacteria.
Data Source
AI summary
The present invention provides β-methyl carbapenem compounds and pharmaceutical compositions useful in the treatment of bacterial infections and methods for treating such infections using such compounds and/or compositions, wherein the compounds are generally of the FormulaeThe invention includes administering an effective amount of a carbapenem compound or salt and/or prodrug thereof to a host in need of such a treatment.